A) Determination of the actions of cytocidal (reo, Mengo, Newcastle disease) and oncogenic (SV40) viruses and of chemical inhibitors on cellular DNA chain initiation and elongation. B) Increased understanding of the function of the proteins in the SV40 DNA-protein complex. C) Test of the hypothesis that interferon production in cells induced with poly(I).poly(C) is restricted through a mechanism involving the synthesis of a repressor mRNA and a labile translation inhibitor. D) Determination of the mechanism of selective action of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) on RNA synthesis. Most of the experiments under A) and B) will be carried out in synchronized populations of MDBK (bovine), L-929 (mouse), 3T3 (mouse), and CV-1 (African green monkey) cells obtained by automated mitotic selection or chemical treatments. Combined use will be made of velocity and density gradient sedimentation techniques, biochemical assays, molecular electron microscopy, and autoradiography. For experiments under C) and D) a wide range of biochemical techniques for the study of RNA and protein synthesis will be employed using FS-4 (human diploid) cells for studies on interferon production and its regulation, and, in addition, L929 (mouse) and HeLa (human) cells for experiments on the precise mechanism of action of dichlorobenzimidazole riboside (DRB). In vitro systems for protein and RNA synthesis will be employed. BIBLIOGRAPHIC REFERENCES: Miller, J.R., Caliguiri, L.A. and Tamm, I. Reaction of poliovirus RNAs with antibodies to double-stranded RNA demonstrated by an immunochemical binding assay. J. Virol. 16: 290-297 (1975). Sehgal, P.B. Tamm, I. and Vilcek, J. Human interferon production: Superinduction by 5,6-dichloro-1-Beta-D-ribofurosylbenzimidazole. Science 190: 282-284 (1975).